Female B6C3F1 mice (6-8 weeks of age) were administered subcutaneous injections of diethylstilbestrol (DES) in corn oil at dosages of 0, 0.2, 2.0 or 8.0 mg/kg body weight for 5 days. Although leukocytosis occurred, there was severe depression of immune functions including antibody responses, delayed hypersensitivity responses, lymphoproliferative responses and numbers of splenic T-cells. Bone marrow examinations revealed hypocellularity and decreased proliferation (colony formation). In contrast, macrophage functions were augmented including production and release of supernatant factors capable of suppressing normal immune function. Host susceptability studies indicated decreased resistance to endotoxin, bacterial infection, tumor cell challenge and parasitemia. In vitro treatment of spleen cells from DES animals with indomethacin inhibited the production of suppressor activity indicating that this factor is prostaglandin.